Global Characterization of Functional Microglia Heterogeneity in Relation to Neovascularization and Regression Phases of Oxygen-Induced Retinopathy in Mice

Retinal neovascularization (RNV) is manifested in various retinal pathological conditions, often leading to irreversible blindness. Oxygen-induced Retinopathy (OIR) mouse model proves to be useful for understanding RNV. The OIR vasculatures exhibited two distinct phases: neovascularization and regression, with microglia playing a pivotal role. Most studies concern microglia functions in promoting RNV; however, global retinal microglia dynamics and functional molecular features during RNV formation and regression have yet to be illustrated. Here, we enriched retinal microglia from normoxia (NOX) and OIR mice retinas at different timepoints of RNV progression and regression and performed single-cell RNA sequencing (scRNA-seq).This approach enabled a detailed analysis of microglia dynamics and functional heterogeneity during retinal neovascularization and regression in OIR mice, providing novel mechanistic insights with potential therapeutic implications for retinal diseases involving pathological neovascularization. Overall design: Microglia from NOX and OIR mice retinas at P17 and P21 were isolated and enriched by CD11b magnetic-activated cell sorting (MACS) and analyzed using scRNA-seq.